DNMT3A-R882 mutations intrinsically drive dysfunctional neutropoiesis from human haematopoietic stem cells
Clonal haematopoiesis (CH) arises from the expansion of hematopoietic stem cells (HSCs) carrying leukaemia-associated somatic mutations. CH is linked to pathological immune dysregulation and a greater risk of age-related inflammatory diseases. Yet, how CH mutations impact HSC differentiation into immune effector cells remains understudied. Here, we report a single-cell resolution functional and multi-omic investigation of HSC clonal and differentiation dynamics in individuals with DNMT3A-R882 CH. DNMT3A-R882 reshapes the clonal architecture of haematopoiesis towards an aged phylogenetic structure. Functionally, DNMT3A-R882 HSCs produce decreased monocytic output but more abundant and mature neutrophil progeny compared to WT HSCs in the same individual. Whereas DNMT3A-R882 myeloid progenitors display attenuated inflammatory transcriptional programmes, DNMT3A-R882 mature neutrophils acquire proinflammatory and immunomodulatory features typical of maladaptive immunity and CH co-morbidities. Our findings, validated in humanised mice, identify aberrant DNMT3A-R882 HSC-driven neutropoiesis as a key link between CH, immune dysregulation and risk of inflammatory disease.
- 16/10/2025
- 1 sample
- DAC: EGAC00001000000
- Technology: Illumina NovaSeq 6000
DUO:0000019 version: 2021-02-23
publication required
This data use modifier indicates that requestor agrees to make results of studies using the data available to the larger scientific community.
DUO:0000026 version: 2021-02-23
user specific restriction
This data use modifier indicates that use is limited to use by approved users.
DUO:0000028 version: 2021-02-23
institution specific restriction
This data use modifier indicates that use is limited to use within an approved institution.
DUO:0000042 version: 2021-02-23
general research use
This data use permission indicates that use is allowed for general research use for any research purpose.
Wellcome Trust Sanger Institute Cancer Genome Group Data Sharing Policy
Studies are experimental investigations of a particular phenomenon, e.g., case-control studies on a particular trait or cancer research projects reporting matching cancer normal genomes from patients.
| Study ID | Study Title | Study Type |
|---|---|---|
| EGAS00001004247 | Cancer Genomics |
This table displays only public information pertaining to the files in the dataset. If you wish to access this dataset, please submit a request. If you already have access to these data files, please consult the download documentation.
| ID | File Type | Size | Quality Report |
Located in
i
|
|---|---|---|---|---|
| EGAF00008943209 | cram | 8.1 GB |
|
|
| EGAF00008943210 | cram | 10.1 GB |
|
|
| EGAF00008943211 | cram | 8.1 GB |
|
|
| EGAF00008943212 | cram | 8.1 GB |
|
|
| EGAF00008943213 | cram | 9.7 GB |
|
|
| EGAF00008943214 | cram | 9.3 GB |
|
|
| EGAF00008943215 | cram | 10.3 GB |
|
|
| EGAF00008943216 | cram | 8.6 GB |
|
|
| EGAF00008943217 | cram | 9.2 GB |
|
|
| EGAF00008943218 | cram | 9.1 GB |
|
|
| EGAF00008943219 | cram | 8.5 GB |
|
|
| EGAF00008943220 | cram | 11.1 GB |
|
|
| EGAF00008943221 | cram | 9.3 GB |
|
|
| EGAF00008943222 | cram | 9.7 GB |
|
|
| EGAF00008943223 | cram | 10.9 GB |
|
|
| EGAF00008943224 | cram | 7.0 GB |
|
|
| EGAF00008943225 | cram | 8.2 GB |
|
|
| EGAF00008943226 | cram | 10.2 GB |
|
|
| EGAF00008943227 | cram | 8.6 GB |
|
|
| EGAF00008943228 | cram | 8.6 GB |
|
|
| EGAF00008943229 | cram | 7.9 GB |
|
|
| EGAF00008943230 | cram | 9.3 GB |
|
|
| EGAF00008943231 | cram | 9.7 GB |
|
|
| EGAF00008943232 | cram | 8.3 GB |
|
|
| EGAF00008943233 | cram | 6.4 GB |
|
|
| EGAF00008943234 | cram | 7.9 GB |
|
|
| EGAF00008943235 | cram | 9.7 GB |
|
|
| EGAF00008943236 | cram | 7.6 GB |
|
|
| EGAF00008943237 | cram | 8.5 GB |
|
|
| EGAF00008943238 | cram | 8.4 GB |
|
|
| EGAF00008943239 | cram | 9.3 GB |
|
|
| EGAF00008943240 | cram | 11.4 GB |
|
|
| EGAF00008943241 | cram | 10.9 GB |
|
|
| EGAF00008943242 | cram | 11.7 GB |
|
|
| EGAF00008943243 | cram | 8.6 GB |
|
|
| EGAF00008943244 | cram | 7.6 GB |
|
|
| EGAF00008943245 | cram | 7.6 GB |
|
|
| EGAF00008943246 | cram | 8.2 GB |
|
|
| EGAF00008943247 | cram | 9.8 GB |
|
|
| EGAF00008943248 | cram | 6.6 GB |
|
|
| EGAF00008943249 | cram | 9.6 GB |
|
|
| EGAF00008943250 | cram | 7.9 GB |
|
|
| EGAF00008943251 | cram | 9.2 GB |
|
|
| EGAF00008943252 | cram | 7.7 GB |
|
|
| EGAF00008943253 | cram | 9.4 GB |
|
|
| EGAF00008943254 | cram | 8.3 GB |
|
|
| EGAF00008943255 | cram | 7.3 GB |
|
|
| EGAF00008943256 | cram | 6.8 GB |
|
|
| EGAF00008943257 | cram | 7.9 GB |
|
|
| EGAF00008943258 | cram | 8.6 GB |
|
|
| EGAF00008943259 | cram | 7.3 GB |
|
|
| EGAF00008943260 | cram | 7.6 GB |
|
|
| EGAF00008943261 | cram | 9.5 GB |
|
|
| EGAF00008943262 | cram | 7.4 GB |
|
|
| EGAF00008943263 | cram | 11.1 GB |
|
|
| EGAF00008943264 | cram | 7.5 GB |
|
|
| EGAF00008943265 | cram | 8.9 GB |
|
|
| EGAF00008943266 | cram | 8.9 GB |
|
|
| EGAF00008943267 | cram | 8.5 GB |
|
|
| EGAF00008943268 | cram | 8.6 GB |
|
|
| EGAF00008943269 | cram | 8.3 GB |
|
|
| EGAF00008943270 | cram | 7.3 GB |
|
|
| EGAF00008943271 | cram | 10.6 GB |
|
|
| EGAF00008943272 | cram | 11.6 GB |
|
|
| EGAF00008943273 | cram | 9.0 GB |
|
|
| EGAF00008943274 | cram | 12.6 GB |
|
|
| EGAF00008943275 | cram | 11.6 GB |
|
|
| EGAF00008943276 | cram | 11.1 GB |
|
|
| EGAF00008943277 | cram | 11.5 GB |
|
|
| EGAF00008943278 | cram | 10.7 GB |
|
|
| EGAF00008943279 | cram | 11.6 GB |
|
|
| EGAF00008943280 | cram | 9.5 GB |
|
|
| EGAF00008943281 | cram | 9.4 GB |
|
|
| EGAF00008943282 | cram | 11.9 GB |
|
|
| EGAF00008943283 | cram | 9.2 GB |
|
|
| EGAF00008943284 | cram | 2.3 GB |
|
|
| EGAF00008943285 | cram | 2.5 GB |
|
|
| EGAF00008943286 | cram | 2.9 GB |
|
|
| EGAF00008943287 | cram | 2.5 GB |
|
|
| EGAF00008943288 | cram | 3.0 GB |
|
|
| EGAF00008943289 | cram | 2.7 GB |
|
|
| EGAF00008943290 | cram | 2.3 GB |
|
|
| EGAF00008943291 | cram | 2.3 GB |
|
|
| EGAF00008943292 | cram | 2.8 GB |
|
|
| EGAF00008943293 | cram | 2.2 GB |
|
|
| EGAF00008943294 | cram | 3.2 GB |
|
|
| EGAF00008943295 | cram | 2.6 GB |
|
|
| EGAF00008943296 | cram | 2.3 GB |
|
|
| EGAF00008943297 | cram | 3.2 GB |
|
|
| EGAF00008943298 | cram | 2.9 GB |
|
|
| EGAF00008943299 | cram | 2.9 GB |
|
|
| EGAF00008943300 | cram | 2.5 GB |
|
|
| EGAF00008943301 | cram | 2.9 GB |
|
|
| EGAF00008943302 | cram | 2.6 GB |
|
|
| EGAF00008943303 | cram | 3.1 GB |
|
|
| EGAF00008943304 | cram | 2.8 GB |
|
|
| EGAF00008943305 | cram | 2.8 GB |
|
|
| EGAF00008943306 | cram | 2.4 GB |
|
|
| EGAF00008943307 | cram | 2.6 GB |
|
|
| EGAF00008943308 | cram | 2.9 GB |
|
|
| EGAF00008943309 | cram | 2.5 GB |
|
|
| EGAF00008943310 | cram | 2.3 GB |
|
|
| EGAF00008943311 | cram | 2.8 GB |
|
|
| EGAF00008943312 | cram | 2.5 GB |
|
|
| EGAF00008943313 | cram | 2.6 GB |
|
|
| EGAF00008943314 | cram | 2.4 GB |
|
|
| EGAF00008943315 | cram | 2.4 GB |
|
|
| EGAF00008943316 | cram | 2.7 GB |
|
|
| EGAF00008943317 | cram | 2.9 GB |
|
|
| EGAF00008943318 | cram | 2.9 GB |
|
|
| EGAF00008943319 | cram | 2.6 GB |
|
|
| EGAF00008943320 | cram | 2.5 GB |
|
|
| EGAF00008943321 | cram | 3.0 GB |
|
|
| EGAF00008943322 | cram | 2.8 GB |
|
|
| EGAF00008943323 | cram | 2.5 GB |
|
|
| EGAF00008943324 | cram | 2.4 GB |
|
|
| EGAF00008943325 | cram | 2.4 GB |
|
|
| EGAF00008943326 | cram | 3.1 GB |
|
|
| EGAF00008943327 | cram | 2.5 GB |
|
|
| EGAF00008943328 | cram | 3.0 GB |
|
|
| EGAF00008943329 | cram | 2.6 GB |
|
|
| EGAF00008943330 | cram | 3.1 GB |
|
|
| EGAF00008943331 | cram | 2.6 GB |
|
|
| EGAF00008943332 | cram | 2.6 GB |
|
|
| EGAF00008943333 | cram | 2.8 GB |
|
|
| EGAF00008943334 | cram | 2.9 GB |
|
|
| EGAF00008943335 | cram | 2.7 GB |
|
|
| EGAF00008943336 | cram | 2.2 GB |
|
|
| EGAF00008943337 | cram | 2.5 GB |
|
|
| EGAF00008943338 | cram | 2.9 GB |
|
|
| EGAF00008943339 | cram | 2.5 GB |
|
|
| EGAF00008943340 | cram | 2.9 GB |
|
|
| EGAF00008943341 | cram | 2.7 GB |
|
|
| EGAF00008943342 | cram | 2.2 GB |
|
|
| EGAF00008943343 | cram | 2.3 GB |
|
|
| EGAF00008943344 | cram | 2.7 GB |
|
|
| EGAF00008943345 | cram | 2.2 GB |
|
|
| EGAF00008943346 | cram | 3.2 GB |
|
|
| EGAF00008943347 | cram | 2.5 GB |
|
|
| EGAF00008943348 | cram | 2.3 GB |
|
|
| EGAF00008943349 | cram | 3.1 GB |
|
|
| EGAF00008943350 | cram | 2.9 GB |
|
|
| EGAF00008943351 | cram | 2.9 GB |
|
|
| EGAF00008943352 | cram | 2.4 GB |
|
|
| EGAF00008943353 | cram | 2.9 GB |
|
|
| EGAF00008943354 | cram | 2.6 GB |
|
|
| EGAF00008943355 | cram | 3.1 GB |
|
|
| EGAF00008943356 | cram | 2.8 GB |
|
|
| EGAF00008943357 | cram | 2.7 GB |
|
|
| EGAF00008943358 | cram | 2.4 GB |
|
|
| EGAF00008943359 | cram | 2.6 GB |
|
|
| EGAF00008943360 | cram | 2.9 GB |
|
|
| EGAF00008943361 | cram | 2.5 GB |
|
|
| EGAF00008943362 | cram | 2.3 GB |
|
|
| EGAF00008943363 | cram | 2.8 GB |
|
|
| EGAF00008943364 | cram | 2.5 GB |
|
|
| EGAF00008943365 | cram | 2.6 GB |
|
|
| EGAF00008943366 | cram | 2.4 GB |
|
|
| EGAF00008943367 | cram | 2.4 GB |
|
|
| EGAF00008943368 | cram | 2.6 GB |
|
|
| EGAF00008943369 | cram | 2.9 GB |
|
|
| EGAF00008943370 | cram | 2.8 GB |
|
|
| EGAF00008943371 | cram | 2.6 GB |
|
|
| EGAF00008943372 | cram | 2.5 GB |
|
|
| EGAF00008943373 | cram | 3.0 GB |
|
|
| EGAF00008943374 | cram | 2.8 GB |
|
|
| EGAF00008943375 | cram | 2.4 GB |
|
|
| EGAF00008943376 | cram | 2.4 GB |
|
|
| EGAF00008943377 | cram | 2.4 GB |
|
|
| EGAF00008943378 | cram | 3.1 GB |
|
|
| EGAF00008943379 | cram | 2.5 GB |
|
|
| EGAF00008943380 | cram | 3.0 GB |
|
|
| EGAF00008943381 | cram | 2.6 GB |
|
|
| EGAF00008943382 | cram | 3.1 GB |
|
|
| EGAF00008943383 | cram | 2.6 GB |
|
|
| EGAF00008943384 | cram | 2.6 GB |
|
|
| EGAF00008943385 | cram | 2.8 GB |
|
|
| EGAF00008943386 | cram | 2.8 GB |
|
|
| EGAF00008943387 | cram | 2.7 GB |
|
|
| EGAF00008943388 | cram | 2.2 GB |
|
|
| EGAF00008943389 | cram | 2.5 GB |
|
|
| EGAF00008943390 | cram | 2.9 GB |
|
|
| EGAF00008943391 | cram | 2.5 GB |
|
|
| EGAF00008943392 | cram | 2.9 GB |
|
|
| EGAF00008943393 | cram | 2.6 GB |
|
|
| EGAF00008943394 | cram | 2.3 GB |
|
|
| EGAF00008943395 | cram | 2.3 GB |
|
|
| EGAF00008943396 | cram | 2.8 GB |
|
|
| EGAF00008943397 | cram | 2.2 GB |
|
|
| EGAF00008943398 | cram | 3.2 GB |
|
|
| EGAF00008943399 | cram | 2.5 GB |
|
|
| EGAF00008943400 | cram | 2.3 GB |
|
|
| EGAF00008943401 | cram | 3.1 GB |
|
|
| EGAF00008943402 | cram | 3.0 GB |
|
|
| EGAF00008943403 | cram | 2.8 GB |
|
|
| EGAF00008943404 | cram | 2.4 GB |
|
|
| EGAF00008943405 | cram | 2.9 GB |
|
|
| EGAF00008943406 | cram | 2.6 GB |
|
|
| EGAF00008943407 | cram | 3.1 GB |
|
|
| EGAF00008943408 | cram | 2.8 GB |
|
|
| EGAF00008943409 | cram | 2.7 GB |
|
|
| EGAF00008943410 | cram | 2.4 GB |
|
|
| EGAF00008943411 | cram | 2.6 GB |
|
|
| EGAF00008943412 | cram | 2.9 GB |
|
|
| EGAF00008943413 | cram | 2.5 GB |
|
|
| EGAF00008943414 | cram | 2.3 GB |
|
|
| EGAF00008943415 | cram | 2.8 GB |
|
|
| EGAF00008943416 | cram | 2.5 GB |
|
|
| EGAF00008943417 | cram | 2.6 GB |
|
|
| EGAF00008943418 | cram | 2.4 GB |
|
|
| EGAF00008943419 | cram | 2.4 GB |
|
|
| EGAF00008943420 | cram | 2.6 GB |
|
|
| EGAF00008943421 | cram | 2.9 GB |
|
|
| EGAF00008943422 | cram | 2.8 GB |
|
|
| EGAF00008943423 | cram | 2.6 GB |
|
|
| EGAF00008943424 | cram | 2.5 GB |
|
|
| EGAF00008943425 | cram | 3.0 GB |
|
|
| EGAF00008943426 | cram | 2.8 GB |
|
|
| EGAF00008943427 | cram | 2.4 GB |
|
|
| EGAF00008943428 | cram | 2.4 GB |
|
|
| EGAF00008943429 | cram | 2.4 GB |
|
|
| EGAF00008943430 | cram | 3.1 GB |
|
|
| EGAF00008943431 | cram | 2.5 GB |
|
|
| EGAF00008943432 | cram | 3.0 GB |
|
|
| EGAF00008943433 | cram | 2.6 GB |
|
|
| EGAF00008943434 | cram | 3.1 GB |
|
|
| EGAF00008943435 | cram | 2.6 GB |
|
|
| EGAF00008943436 | cram | 2.6 GB |
|
|
| EGAF00008943437 | cram | 2.8 GB |
|
|
| EGAF00008943438 | cram | 2.8 GB |
|
|
| EGAF00008943439 | cram | 2.6 GB |
|
|
| 231 Files (1.1 TB) | ||||